Reflections and Roadmaps: Career Development beyond the FDA-AACR Oncology Educational Fellowship.

In 2020, the FDA's Oncology Center of Excellence, in collaboration with the American Association for Cancer Research, launched a novel educational partnership known as the FDA-AACR Oncology Educational Fellowship. This year-long program is aimed for hematology/oncology fellows, scientists, and early-career investigators, offering an in-depth exploration of the regulatory review process by blending didactic learning with practical cases discussing oncology drug approvals. The fellowship has been met with enthusiastic feedback, with participants lauding its role in demystifying the regulatory landscape and enhancing their professional careers.

Inflammatory Markers of the Systemic Capillary Leak Syndrome (Clarkson Disease).

Objectives: The Systemic Capillary Leak Syndrome (SCLS) is a rare and potentially fatal disorder resembling systemic anaphylaxis that is characterized by transient episodes of hypotensive shock and peripheral edema. The pathogenesis of SCLS is unknown, and triggers for attacks are apparent only in a minority of patients. We introduce a clinical algorithm for the diagnosis of SCLS, and we investigated potential serum biomarkers of acute SCLS episodes.

Mastocytosis associated with a rare germline KIT K509I mutation displays a well-differentiated mast cell phenotype.

Background: Mastocytosis associated with germline KIT activating mutations is exceedingly rare. We report the unique clinicopathologic features of a patient with systemic mastocytosis caused by a de novo germline KIT K509I mutation.

Objectives: We sought to investigate the effect of the germline KIT K509I mutation on human mast cell development and function.

Diminished allergic disease in patients with STAT3 mutations reveals a role for STAT3 signaling in mast cell degranulation.

Background: Severe atopic conditions associated with elevated serum IgE are heterogeneous with few known causes. Nearly every patient with autosomal-dominant hyper-IgE syndrome (AD-HIES) due to signal transducer and activator of transcription 3 (STAT3) mutations has a history of eczematous dermatitis and elevated IgE; however, clinical atopy has never been systematically studied.

Objective: Understanding of genetic determinants of allergic disease may lead to novel therapies in controlling allergic disease.

Cold urticaria, immunodeficiency, and autoimmunity related to PLCG2 deletions.

Background: Mendelian analysis of disorders of immune regulation can provide insight into molecular pathways associated with host defense and immune tolerance.

Methods: We identified three families with a dominantly inherited complex of cold-induced urticaria, antibody deficiency, and susceptibility to infection and autoimmunity. Immunophenotyping methods included flow cytometry, analysis of serum immunoglobulins and autoantibodies, lymphocyte stimulation, and enzymatic assays.

Selective depletion of alloreactive donor lymphocytes: a novel method to reduce the severity of graft-versus-host disease in older patients undergoing matched sibling donor stem cell transplantation.

We have selectively depleted host-reactive donor T cells from peripheral blood stem cell (PBSC) transplant allografts ex vivo using an anti-CD25 immunotoxin. We report a clinical trial to decrease graft-versus-host disease (GVHD) in elderly patients receiving selectively depleted PBSC transplants from HLA-identical sibling donors. Sixteen patients (median age, 65 years [range, 51-73 years]), with advanced hematologic malignancies underwent transplantation following reduced-intensity conditioning with fludarabine and either cyclophosphamide (n = 5), melphalan (n = 5), or busulfan (n = 6).

A pilot study of the recombinant soluble human tumour necrosis factor receptor (p75)-Fc fusion protein in patients with myelodysplastic syndrome.

Laboratory observations suggest that, in some myelodysplastic syndromes (MDS), immune mechanisms may contribute to the impaired blood cell production. Tumor necrosis factor alpha (TNF-alpha), a potent inhibitor of haematopoiesis, has been hypothesized to mediate suppressive effects in MDS: TNF-alpha levels are elevated and correlated with marrow apoptosis and cytopenia. Inhibition of TNF-alpha production using the soluble TNF receptor (Enbrel) has been successful in rheumatoid arthritis, and we have now applied the same principle to MDS.